Nerve-growth agent could treat incontinence caused by spinal cord injury

Image of Rosalyn Adam, a urology researcher hoping to develop new treatments for incontinence, working in the laboratory
Rosalyn Adam is the director of urology research at Boston Children’s Hospital.

When the nerves between the brain and the spinal cord aren’t working properly, bladder control can suffer, resulting in a condition called neurogenic bladder. It’s a common complication of spinal cord injury; in fact, most people with spina bifida or spinal cord injury develop neurogenic bladders. Spontaneous activity of the smooth muscle in the wall of the bladder — called the detrusor muscle — commonly causes urine leakage and incontinence in people with neurogenic bladders.

“For children and adults, incontinence can be one of the most socially and psychologically detrimental complications of spinal cord injury,” says Rosalyn Adam, PhD, who is director of urology research at Boston Children’s Hospital. “The ultimate goal of our research is to return bladder control to the millions of Americans with neurogenic bladders.”

Now, Adam and a team of researchers think that they may have found a practical way to treat neurogenic detrusor overactivity by delivering medication directly into the bladder through self-catheterization, a practice that many people with neurogenic bladders already need to perform regularly.

An incontinence therapy designed for the daily routine

In a recent paper, published in Scientific Reports, Adam’s team showed that a naturally-occurring molecule called inosine, delivered into the bladder, was able to reduce spontaneous detrusor activity in rats.

Inosine was first investigated in the context of treating neurologic injury by Larry Benowitz, PhD, director of the Laboratories for Neuroscience Research in Neurosurgery at Boston Children’s. When delivered directly into brain ventricles or intravenously in rat models, inosine enhanced nerve fiber (axon) growth, synaptic connections and motor recovery from spinal cord injury. The group’s earlier work had also shown strong effects in improving outcome after stroke.  Encouraged by recent evidence from other labs, Benowitz hopes to move to translational studies, as data indicating inosine’s safety are already available.

Inosine, which promotes nerve growth, is already available as a nutritional supplement and was found to be safe and tolerable in a clinical trial investigating its use in treating Parkinson’s disease.

Although inosine has been shown to provide neuroprotective effects when given systemically, the team’s local-delivery approach could reduce side effects throughout the rest of the body. It could also allow patients to administer the drug themselves as part of their daily routine, rather than requiring them to visit the clinic for intravenous delivery.

A chance to improve people’s lives

Now, in partnership with Carlos Estrada, MD, MBA, who is a urologist and director of the Spina Bifida Center at Boston Children’s, Adam hopes to develop a clinical trial protocol that could enable inosine to start improving people’s lives.

“Increasingly, I’m seeing that patients and their families are concerned about the side effects — which can include constipation, dry mouth, flushing, overheating and even cognitive changes — of the systemic medications that are currently being used to treat neurogenic bladder,” Estrada says.

Estrada has also co-founded a start-up company offering a biofeedback product for reducing incontinence. 

That makes a potential treatment strategy that could avoid those side effects very attractive, Estrada explains.

“Since most patients with neurogenic bladder already need to intermittently self-catheterize, a once-a-day administration of inosine directly into the bladder would have a low impact on daily routine but could help reduce incontinence in a doable, effective manner,” Estrada concludes.